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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0407213

Received for publication April 6, 2007.
Revised May 10, 2007.
Accepted for publication May 10, 2007.

Article

Low-density cells isolated from the rat thymus resemble branched cortical macrophages and have a reduced capability of rescuing double-positive thymoctyes from apoptosis in the BB-DP rat

Vinod Sommandas *@, Elizabeth A. Rutledge {dagger}, Brian Van Yserloo {dagger}, Jessica Fuller {dagger}, Åke Lernmark {dagger}, and Hemmo A. Drexhage *{dagger}

*Department of Immunology, Erasmus MC, Rotterdam, The Netherlands; and {dagger}Department of Medicine, R.H. Williams Laboratory, University of Washington, Seattle, Washington, USA

@ To whom correspondence should be addressed. E-mail: v.sommandas{at}erasmusmc.nl.


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Abstract

Biobreeding-diabetes prone (BB-DP) rats spontaneously develop organ-specific autoimmunity and are severely lymphopenic and particularly deficient in ART2+ regulatory T cells. A special breed, the so-called BB-diabetic-resistant (DR) rats, are not lymphopenic and do not develop organ-specific autoimmunity. The genetic difference between both strains is the lymphopenia (lyp) gene. Intrathymic tolerance mechanisms are important to prevent autoimmunity, and next to thymus epithelial cells, thymus APC play a prominent part in this tolerance. We here embarked on a study to detect defects in thymus APC of the BB-DP rat and isolated thymus APC using a protocol based on the low-density and nonadherent character of the cells. We used BB-DP, BB-DR, wild-type F344, and F344 rats congenic for the lyp gene-containing region. The isolated thymus, nonadherent, low-density cells appeared to be predominantly ED2+ branched cortical macrophages and not OX62+ thymus medullary and cortico-medullary dendritic cells. Functionally, these ED2+ macrophages were excellent stimulators of T cell proliferation, but it is more important that they rescued double-positive thymocytes from apoptosis. The isolated thymus ED2+ macrophages of the BB-DP and the F344.lyp/lyp rat exhibited a reduced T cell stimulatory capacity as compared with such cells of nonlymphopenic rats. They had a strongly diminished capability of rescuing thymocytes from apoptosis (also of ART2+ T cells) and showed a reduced Ian5 expression (as lyp/lyp thymocytes do). Our experiments strongly suggest that branched cortical macrophages play a role in positive selection of T cells in the thymus and point to defects in these cells in BB-DP rats.

Key Words: type I diabetes • autoimmunity • positive selection